During the previous funding period, reported having developed a new medical imaging paradigm called thermoacoustic CT (TCT). In its current implementation, TCT utilizes brief pulses of radio waves at 434 MHz to stimulate acoustic emissions in soft tissue. These sonic emissions are detected by an array of piezo-electric crystals and are recorded temporally following each of 250,000 individual RF pulses. From the recorded sonic emissions, patterns of radio-wave absorption within the soft tissue volume are reconstructed in three dimensions. The applicants reported having demonstrated good soft tissue differentiation in an excised porcine kidney, and we have successfully imaged breast cancer in vivo. The goal of the proposed research program is to better understand the underlying RF-absorption properties of soft tissue, and to improve the current TCT instrumentation for imaging the human breast. To these ends, the following specific aims will be pursued during the proposed three-year funding period: 1. Relate the properties of specific heart, volume thermal expansion and complex permittivity to TCT image contrast: 2. Relate bound water fraction to TCT image contrast; 3. Correlate the physiologic properties of different breast tumor cell lines with TCT image contrast; 4. Develop simulation tools to predict and validate TCT imaging performance in the breast; 5. Design, construct and test an improved TCT breast scanner; and 6. Perform retrospective TCT imaging on small groups of patients